A common reaction for making polymers is free radical polymerisation, which is used to make polymers from unsaturated monomers, for example styrene and/or acrylates. Free radical polymerisation may be performed by emulsion polymerisation or suspension polymerisation. Emulsion polymerisation is the standard process for production of polymer particles in sizes around 100-500 nm. The product is often called a latex and is the main component of water based paints. In emulsion polymerisation unsaturated monomers are, as just mentioned, converted to polymers by the use of free radical polymerisation. Typically the polymerisation is carried out in water and the monomers have a low water solubility.
In a typical procedure, a monomer such as styrene, for example, is mixed with water and surfactants and the mix is stirred to make relatively large styrene droplets (1-10 μm). A water soluble initiator is added. The initiator decomposes to two radicals and starts reacting with the monomers that have been solubilised in the water phase. In the case of styrene, the growing chain soon becomes water insoluble and the molecules aggregate to nanometer-sized particles. If the initiation phase is short the resulting particles can be monosized.
The particles then grow by the following mechanism: The monomers diffuse through the water phase into the polymer particles. The polymerisation in the particles is initiated by the adsorption of growing polymers from the water phase. Since the particles are so small only one radical can survive in the particle at the same time, and the adsorption of a second growing chain will therefore result in termination. The polymerisation stops when the monomer in the large droplets has diffused into the growing particles and polymerised.
Emulsion polymerisation is dependent on the transfer of monomer from the large droplets to the smaller particles and radical adsorption. If a high amount of crosslinking monomer is used—that is above 10-15%—the small particles will be crosslinked and the polymerisation does not continue.
Emulsion polymerisation is used to produce monosized seed particles as starting material for the Ugelstad two step swelling process.
This application teaches a method which is able to produce submicron highly crosslinked polymer particles which it is believed cannot be obtained by emulsion polymerisation. It is known to produce cross-linked porous or solid monodisperse polymer particles by a two stage process, named the Ugelstad process after the late Professor John Ugelstad, which is described for example in EP-B-3905 (Sintef) and U.S. Pat. No. 4,530,956 (Ugelstad). An improved Ugelstad process is described in WO 00/61647. In the Ugelstad process, seed particles, suitably made by emulsion polymerisation, are converted in two steps into monodisperse particles by seeded suspension polymerisation. In a first step, the seed particles are swollen by making a fine (e.g. submicron) aqueous emulsion of a relatively low molecular weight water-insoluble substance and then adding a water-miscible organic solvent (e.g. acetone) so that the water-insoluble substance diffuses into the seed particles. It is convenient for the water-insoluble substance to be a heat-activated polymerisation initiator. In a second step, the solvent is then removed, locking the water-insoluble substance in the seed particles, and the seed particles take up a large quantity of monomer and also a cross-linker, driven by an increase in entropy when the monomer and cross-linker diffuse into the seed particles and dilutes the water-insoluble substance. In practice, after the seed particles have been swollen and absorbed the water-insoluble substance, the dispersion containing them is typically contacted with an aqueous emulsion containing the monomer and cross-linker; the amount of water is chosen to be sufficient for the water to act to remove the water-miscible solvent by dilution and the monomer is driven into the seed particles. The seed particles swell and, following initiation of polymerisation, e. g. by heating to activate the initiator, larger polymer particles are produced. The Ugelstad process therefore comprises making seed particles by emulsion polymerisation and expanding the seed particles by suspension polymerisation. The smallest monodisperse particles described in the aforementioned prior art have an average diameter of 1 μm.
A porogen may be contacted with the seed particles in the final swelling and polymerisation stage in order to make the particles porous. A porogen is an organic liquid which does not participate in the polymerisation reaction. It may be a good solvent for the polymer in which case it will make small pores, or a poor solvent for the polymer, in which case it will form large pores. The present inventors have not been able to control the pore morphology of submicron beads to provide a smooth outer surface by selection of porogens.
In a simplified version of the Ugelstad process, the enhanced capacity for swelling may be achieved simply by the use of oligomeric seed particles, e.g. where the oligomer weight average molecular weight corresponds to up to 50 monomer units (a molecular weight of about 5000 in the case of polystyrene).
Conveniently, a very fine submicron (e.g. 0.05-0.5 μm) stable oil-in-water emulsion can be made if there is used as the emulsifier a combination of a water-soluble surfactant and a less water soluble organic compound. The surfactant is usually ionic but alternatively may be non-ionic.
Prior art Ugelstad methods described above do not provide smooth monodisperse porous particles at small particle sizes. In particular, the prior art methods do not produce smooth particles at the lower size limits. Instead, the outer surface of these small porous particles would be irregular and, for example appear rough or knobbly when viewed at a magnification of e.g. 10,000, e.g. when compared to larger particles. This rough appearance is caused by the morphology of the pores, e.g. excessive pore size.